Dithiocarbamates are a class of chemical compounds enjoying wide use in industry, agriculture, and medicine. Most of them are potent chelating agents. As chelators, however, they may also promote elevated brain levels of metals at the same time that they enhance excretion from other organ systems. Lead, copper, nickel, methylmercury, cadmium, and thallium are among the metals for which such effects have been shown. Whether these elevated brain levels might also induce neurotoxicity, and under what circumstances, needs to be clarified. The proposed research represents an effort to combine chemical and behavioral measures to explore these issues. Rats will be exposed to lead, nickel, and thallium in drinking water and treated twice weekly with diethyldithiocarbamate (DDC). Chemical measures will be used to ascertain metal levels in various tissues, whether the metal is bound to DDC in the tissue or is in another form, and to determine a variety of biochemical effects. Behavioral measures, derived from a modified running wheel apparatus, will be used trace the appearance of neurotoxicity during the different treatment regimens.